Carbamate Toxicity - An Overview

Introduction

Acetylcholinesterase, an enzyme found at the neuromuscular junction (junction between a neuron and muscle fiber) is carbamylated (modified) by carbamates. These are N-methyl carbamates generated from a carbamic acid, in neuronal synapses and neuromuscular junctions. While carbamates bind to acetylcholinesterase reversibly, they share a similar mode of action with the irreversible phosphorylation by organophosphates (OP). Hence, carbamates have a toxicological presentation comparable to OP poisonings, with a specific toxicity period of fewer than 24 hours. Aldicarb, carbofuran, carbaryl, methomyl, pirimicarb, propoxur, and trimethacarb are common agents that cause hazardous exposure.

What Are the Causes of Carbamate Toxicity?

• Dermal, inhalational, and gastrointestinal (GI) exposures to toxic carbamates are possible. Based on data from rat oral LD 50, the World Health Organization (WHO) classification of pesticides divides chemicals into five categories. The classification of the pesticide and the exposure dose affect the severity of the symptoms.

• The most frequent causes of carbamate poisoning are deliberate oral consumption or occupational cutaneous exposure. Large outbreaks caused by tainted food and crops have been documented in developing nations.

• According to the pharmacokinetics of the different carbamates, cutaneous exposure may cause symptoms to appear quickly. After working in regions recently sprayed or fogged with pesticides, exposure can occur from mixed cutaneous and inhalational exposures.

How Common Is Carbamate Toxicity?

There is no industry regulation of pesticides in underdeveloped nations. Local agricultural practices are free to employ toxic pesticides, increasing the risk of serious, unintended job exposures and toxicity following self-harm. An estimated 200,000 fatalities per year are attributed to the intentional self-injurious behaviors caused by carbamate and organophosphates in rural Asia. Modeling results predict one to two million cases in rural Asia annually, with 20 to 30 % of patients expected to experience respiratory failure due to purposeful carbamate and OP exposures. It is estimated that these two types of pesticides together need between 1 million and 2 million ventilation days annually. They bear a significant portion of the cost of illness and mortality.

What Is the History of Carbamate?

To identify carbamate poisoning, there must be a strong degree of suspicion based on historical characteristics and the existence of a clinical toxidrome. Individuals with central nervous system (CNS) poisoning may have changed mental status and cannot give a thorough history when they are first seen. Due to the same symptoms of acute poisoning, the initial treatment for carbamate and OP toxicity will be the same. If more historians are available, it may be possible to determine which class of pesticide the patient was exposed to by looking up the substances that were either intentionally consumed or were a part of the accidental exposures on a Material Safety and Data Sheet.

The examination findings of hypersalivation (excessive flow of saliva), lacrimation (flow of tears), gastrointestinal distress, and diaphoresis (sweating) support the diagnosis. Due to the simultaneous stimulation of the parasympathetic and sympathetic nervous systems, patients may exhibit bradycardia (slow heart rate), tachycardia (rapid heart rate), miosis (excessive constriction of the pupil of the eye), and their pupil examination may reveal these conditions. When patients appear with pin-point pupils, heavy perspiration, and breathing difficulties, OP and carbamate poisoning should be considered for the differential diagnosis. Neuropathy may become chronic.

What Is the Treatment of Carbamate Toxicity?

Carbamate toxicity can adversely affect the following areas:

Decontamination:

• Decontamination needs to happen as quickly as feasible due to the ongoing cutaneous absorption of carbamate insecticides. Medical professionals should wear personal protective equipment (PPE) to prevent self-contamination. Gloves made of nitrile or neoprene offer sufficient protection against cutaneous exposures. The healthcare provider should wear full protective equipment, at least a gown, mask, and face shield. Insecticide protection from latex gloves is insufficient.

• The patients should be stripped of all clothing, and their skin should be cleaned three times; once with water, once with soap, and once again with water. Gastrointestinal ingestions, vomiting, and diarrhea may lead to cutaneous absorption in healthcare professionals.

• If the patient has not experienced episodes of vomiting, gastrointestinal (GI) decontamination may be considered insignificant, in life-threatening ingestions. Nasogastric lavage may be used in this situation.

• Patients may have seizures, respiratory paralysis, and coma in cases of severe poisoning. If these characteristics are present, airway protection should follow GI decontaminates.

• If the patient arrives within an hour of a huge, life-threatening gastrointestinal consumption, giving a single dosage of 1 g/kg activated charcoal is advised. Consulting a local toxicologist or poison center before gastrointestinal decontamination may be a sensible course of action.

Respiratory Support:

• Respiratory failure and hypoxia are the primary cause of death following hazardous exposure to AChE inhibitors.

• Muscular deterioration, possible flaccid paralysis, and CNS respiratory drive depression are secondary causes of this complex condition.

• First, patient evaluation after decontamination should ensure the patient gets enough oxygen and ventilation. Atropine can reduce increased respiratory secretions by competitively inhibiting the overexcitation of muscarinic receptors.

• Patients with trouble controlling their respiratory secretions, comatose or extremely depressed mental condition, or considerable skeletal muscle weakness should have early endotracheal intubation.

• Succinylcholine and other depolarizing neuromuscular blockers should be avoided since they can cause protracted paralysis that can linger for several hours because AChE inhibitors inactivate serum cholinesterases. Instead, nondepolarizing neuromuscular blockers like Rocuronium should be used to cause paralysis.

Atropine:

• Atropine reduces symptoms of lacrimation, salivation, miosis, emesis, diarrhea, diaphoresis, urine incontinence, bronchospasm, and excessive respiratory secretions by competitively antagonizing the elevated acetylcholine levels at muscarinic receptors.

• Atropine should be provided starting at 1 to 3 milligrams (mg) intravenously (IV) for adults or 0.05 mg/kg IV for children with a minimum dose of 0.1 milligrams. If the initial dose doesn't respond sufficiently, the dose should be raised every five minutes. The treatment should be focused on achieving cardiorespiratory stability because previous descriptions of "atropinization" (dry skin and mucous membranes, decreased bowel sounds, tachycardia, a lack of bronchospasm, and mydriasis) did not emphasize important outcomes of resuscitation.

• When there is a reduction in tracheobronchial secretions and bronchoconstriction, good blood pressure, and heart rate for tissue perfusion, an appropriate dose of atropine is administered.

• A steady infusion of atropine, typically 10 to 20 percent of the bolus dose each hour, is used to maintain the therapy response once a stable dose of atropine has been reached.

• In patients presenting with carbamate poisoning, tachycardia is not a contraindication to treating atropine because tachycardia may be attributable to hypoxia and extensive bronchopulmonary secretions.

• For treating severe AChE inhibitor poisonings, doses of above 1000 mg of atropine have been observed over 24 hours. The skeletal and muscular weakness brought on by nicotinic receptor stimulation in carbamate poisoning cannot be reversed by atropine.

Conclusion

The most common causes of carbamate poisoning are deliberate oral consumption or occupational cutaneous exposure. Increased acetylcholine levels at the parasympathetic and sympathetic nervous system, the central nervous system, and nicotinic receptors in skeletal muscle tissue all contribute to carbamate poisoning. Therefore, the emergency department should be a part of the interprofessional team that diagnoses and manages carbamate poisoning.